15-hydroxyprostaglandin dehydrogenase (NAD+)

Class of enzymes hydroxyprostaglandin dehydrogenase 15-(NAD) 1.1.1.141 9030-87-9 0016404 2gdz.jpg 270 15-hydroxyprostaglandin dehydrogenase dimer (NAD dependent), Human Hydroxyprostaglandin dehydrogenase 15-(NAD) (the HUGO-approved symbol = HPGD; HGNC ID, HGNC:5154), also called 15-hydroxyprostaglandin dehydrogenase (NAD+), (1.1.1.141), is an enzyme produced by the HPGD gene. Function It catalyzes the NAD⁺-dependent oxidation of the 15-hydroxyl group of prostaglandins (primarily prostaglandin E2 or PGE2, but also others like PGD2 and PGF2α) and related eicosanoids (such as lipoxins), converting them to inactive 15-keto metabolites. This is the rate-limiting step in prostaglandin degradation, reducing their biological activity and regulating processes such as inflammation, cell proliferation, and tissue homeostasis.:1.1.1.141Huang Wei Li Hongyun Kiselar Janna Fink Stephen P. Regmi Sagar Day Alexander Yuan Yiyuan Chance Mark Ready Joseph M. Markowitz Sanford D. Taylor Derek J. 2023-02-11 Small molecule inhibitors of 15-PGDH exploit a physiologic induced-fit closing system Nature Communications en 14 1 784 10.1038/s41467-023-36463-7 free 36774348 9922282 2023NatCo..14..784H 2041-1723 60% prostaglandin E2 + NAD+ reversible H+ H+ Q27098095 15-ketoprostaglandin E2 + NADH Biological Role Downregulation in cancer — Can be reduced in tumors (e.g., colorectal, lung, breast), leading to elevated PGE2 levels that promote tumorigenesis; it acts as a tumor suppressor.Tai Hsin-Hsiung Tong Min Ding Yunfei May 2007 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and lung cancer Prostaglandins & Other Lipid Mediators 83 3 203–208 10.1016/j.prostaglandins.2007.01.007 1098-8823 1963423 17481556 Aging and regeneration — Levels increase with age, contributing to tissue decline (e.g., muscle atrophy, cartilage loss). Inhibiting 15-PGDH elevates PGE2 and promotes regeneration in muscle, bone, cartilage, liver, colon, and hematopoietic tissues.Conger Krista 2025-11-27 Inhibiting a master regulator of aging regenerates joint cartilage in mice https://med.stanford.edu/news/all-news/2025/11/joint-cartilage-aging.html 2026-01-05 News Center en-USDesai Amar 2023-11-02 15-Pgdh Inhibition Alternatively Activates Macrophages to Promote Hematopoietic Function during Aging https://ashpublications.org/blood/article/142/Supplement%201/5610/506001/15-Pgdh-Inhibition-Alternatively-Activates Blood en 142 Supplement 1 5610 10.1182/blood-2023-174704 0006-4971 https://web.archive.org/web/20240407032923/https://ashpublications.org/blood/article/142/Supplement%201/5610/506001/15-Pgdh-Inhibition-Alternatively-Activates 2024-04-07 subscription 2026-01-05 live Inflammation and immunity — Degrades pro-inflammatory prostaglandins; inhibition can enhance resolution of inflammation or protect barriers like the blood-brain barrier in conditions such as Alzheimer's or traumatic brain injury.Koh Yeojung Vázquez-Rosa Edwin Gao Farrah Li Hongyun Chakraborty Suwarna Tripathi Sunil Jamuna Barker Sarah Bud Zea Bangalore Anusha Kandjoze Uapingena P. León-Alvarado Rose A Sridharan Preethy S. Cordova Brittany A. Yu Youngmin Hyung Jiwon 2025-05-27 Inhibiting 15-PGDH blocks blood–brain barrier deterioration and protects mice from Alzheimer's disease and traumatic brain injury Proceedings of the National Academy of Sciences 122 21 e2417224122 10.1073/pnas.2417224122 12130856 40397680 2025PNAS..12217224K Other roles — It is involved in wound healing, obesity-related inflammation, and pregnancy maintenance. Therapeutic interest Small-molecule inhibitors of 15-PGDH are under investigation for promoting tissue repair, countering sarcopenia, treating osteoarthritis, and supporting recovery after injury or transplantation. Mutations in HPGD can cause rare disorders like primary hypertrophic osteoarthropathy (digital clubbing, bone overgrowth).What are 15-PGDH inhibitors and how do they work? https://synapse.patsnap.com/article/what-are-15-pgdh-inhibitors-and-how-do-they-work 2026-01-05 synapse.patsnap.com en Ligands Inhibitors SW033291Zhang Yongyou Desai Amar Yang Sung Yeun Bae Ki Beom Antczak Monika I. Fink Stephen P. Tiwari Shruti Willis Joseph E. Williams Noelle S. Dawson Dawn M. Wald David Chen Wei-Dong Wang Zhenghe Kasturi Lakshmi Larusch Gretchen A. He Lucy Cominelli Fabio Di Martino Luca Djuric Zora Milne Ginger L. Chance Mark Sanabria Juan Dealwis Chris Mikkola Debra Naidoo Jacinth Wei Shuguang Tai Hsin-Hsiung Gerson Stanton L. Ready Joseph M. Posner Bruce 1 Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration Science 2015 348 6240 aaa2340 10.1126/science.aaa2340 26068857 4481126 Mallipeddi Prema L. Zhang Yongyou Li Hongyun Markowitz Sanford D. Posner Bruce Structural Insights into Novel 15-Prostaglandin Dehydrogenase Inhibitors Molecules 2021 26 19 5903 10.3390/molecules26195903 free 34641449 8512612 Singla Mamta Wang Yu Xin Monti Elena Bedi Yudhishtar Agarwal Pranay Su Shiqi Ancel Sara Hermsmeier Maiko Devisetti Nitya Pandey Akshay Bakooshli Mohsen Afshar Palla Adelaida R. Goodman Stuart Blau Helen M. Bhutani Nidhi Inhibition of 15-hydroxy prostaglandin dehydrogenase promotes cartilage regeneration Science 2025 eadx6649 10.1126/science.adx6649 SW209415Desai Amar Zhang Yongyou Park Youngsoo Dawson Dawn M. Larusch Gretchen A. Kasturi Lakshmi Wald David Ready Joseph M. Gerson Stanton L. Markowitz Sanford D. A second-generation 15-PGDH inhibitor promotes bone marrow transplant recovery independently of age, transplant dose and granulocyte colony-stimulating factor support Haematologica 2018 103 6 1054–1064 10.3324/haematol.2017.178376 29472361 6058768 SW222746 ML148Niesen Frank H. Schultz Lena Jadhav Ajit Bhatia Chitra Guo Kunde Maloney David J. Pilka Ewa S. Wang Minghua Oppermann Udo Heightman Tom D. Simeonov Anton High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships PLOS ONE 2010 5 11 e13719 10.1371/journal.pone.0013719 free 21072165 2010PLoSO...513719N 2970562 15-PGDH-IN-4 Dodda Leela S. Campos Sebastien Ciccone David Carreiro Samantha Leit Silvana Brennan Debra Zephyr Jacqueto Jacques-o'Hagan Suzanne Kumar Sheetal Kuo Fu-Shan Shaik Md Munan Price Daniel J. Loh Christine Edmondson Scott D. Tummino Peter Kaila Neelu Knowledge and Structure-Based Drug Design of 15-PGDH Inhibitors Journal of Medicinal Chemistry 2025 68 17 18436–18462 10.1021/acs.jmedchem.5c01231 40864846 HW201877Li Qun Zang Yang An Dan Yin Shanshan Wu Haomiao Wang Meng Li Chao Zhou Yuan Liu Lifei Zhang Xuejun Discovery of HW201877: A Highly Potent and Orally Bioavailable Inhibitor of 15-Prostaglandin Dehydrogenase to Potentiate Tissue Repair and Regeneration Journal of Medicinal Chemistry 2025 68 13 14099–14113 10.1021/acs.jmedchem.5c01361 40568827 Substrates The two substrates of this enzyme are prostaglandin E2 and oxidised nicotinamide adenine dinucleotide (NAD+). Its products are 15-ketoprostaglandin E2, reduced NADH, and a proton.Anggaard E, Samuelsson B 1966 Purification and properties of a 15-hydroxyprostaglandin dehydrogenase from swine lung Prostaglandins 25 293–300 Braithwaite SS, Jarabak J 1975 Studies on a 15-hydroxyprostaglandin dehydrogenase from human placenta. Purification and partial characterization J. Biol. Chem. 250 2315–8 1117007 6 10.1016/S0021-9258(19)41718-3 free Lee SC, Levine L 1975 Prostaglandin metabolism. II. Identification of two 15-hydroxyprostaglandin dehydrogenase types J. Biol. Chem. 250 548–52 234431 2 10.1016/S0021-9258(19)41931-5 free Lee SC, Pong SS, Katzen D, Wu KY, Levine L 1975 Distribution of prostaglandin E 9-ketoreductase and types I and II 15-hydroxyprostaglandin dehydrogenase in swine kidney medulla and cortex Biochemistry 14 142–5 803247 10.1021/bi00672a024 1 Class This enzyme belongs to the family of oxidoreductases, specifically those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is (5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprost-13-enoate:NAD+ 15-oxidoreductase. Other names in common use include NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (type I), PGDH, 11alpha,15-dihydroxy-9-oxoprost-13-enoate:NAD+ 15-oxidoreductase, 15-OH-PGDH, 15-hydroxyprostaglandin dehydrogenase, 15-hydroxyprostanoic dehydrogenase, NAD+-specific 15-hydroxyprostaglandin dehydrogenase, prostaglandin dehydrogenase, 15-hydroxyprostaglandin dehydrogenase (NAD+), and 15-PGDH. Structural studies As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code 2GDZ. References 1 Biology no Category:EC 1.1.1 Category:NADH-dependent enzymes Category:Enzymes of known structure Category:Long stubs with short prose